Targeted therapeutics

Schema of nanoparticle fabrication to knockdown Kv1.3 channels (Hajdu et al., 2013)

One of our laboratory research interest is to develop nanoparticles for target delivery of siRNAs to specific T cell subsets. We have fabricated lipid nanoparticles to knock-down Kv1.3 channels in memory T lymphocytes to be used as novel immunosuppressive agents with limited side effects. These highly versatile scaffoldings can be tailored to individual patient needs for personalized medicine. We have shown their efficacy in vitro and we are now studying their efficacy in vivo in humanized mouse models of SLE. Further nanoparticles are currently been developed as novel targeted immunotherapies in cancer.

Kv1.3 nanoparticles visualized by imaging flow cytometry (Chimote et al., 2016)

Relevant Publications:

Khodoun M, Chimote AA, Ilyas FZ, Duncan HJ, Moncrieffe H, Kant KS, Conforti L. Targeted knockdown of Kv1.3 channels in T lymphocytes corrects the disease manifestations associated with systemic lupus erythematosus Sci Adv. 2020 Nov 18;6(47):eabd1471. doi: 10.1126/sciadv.abd1471.

Chimote A.A., Hajdu P., Kottyan L.C., Harley J.B., Yun Y-H and Conforti L. Nanovesicle-targeted Kv1.3 knockdown in memory T cells suppresses CD40L expression and memory phenotype. J Autoimmun. 2016 May; 69:86-93. doi: 10.1016/j.jaut.2016.03.004. Epub 2016 Mar 16. PMID: 26994905.

Hajdu P., Chimote A.A., Thompson T., Koo Y., Yun Y-H. and Conforti L., Functionalized liposomes loaded with siRNAs targeting ion channels in effector memory T cells as a potential therapy for autoimmunity. Biomaterials 34, pp. 10249-10257, 2013. DOI information: 10.1016/j.biomaterials.2013.09.019. PMID: 24075407 PMCID: PMC3900865.